Erratum in

Abstract

The perception of touch, including the direction of stimulus movement across the skin, begins with activation of low-threshold mechanosensory neurons (LTMRs) that innervate the skin. Here, we show that murine Aδ-LTMRs are preferentially tuned to deflection of body hairs in the caudal-to-rostral direction. This tuning property is explained by the finding that Aδ-LTMR lanceolate endings around hair follicles are polarized; they are concentrated on the caudal (downward) side of each hair follicle. The neurotrophic factor BDNF is synthesized in epithelial cells on the caudal, but not rostral, side of hair follicles, in close proximity to Aδ-LTMR lanceolate endings, which express TrkB. Moreover, ablation of BDNF in hair follicle epithelial cells disrupts polarization of Aδ-LTMR lanceolate endings and results in randomization of Aδ-LTMR responses to hair deflection. Thus, BDNF-TrkB signaling directs polarization of Aδ-LTMR lanceolate endings, which underlies direction-selective responsiveness of Aδ-LTMRs to hair deflection.

(A) Pregnant TrkBCreER/+;Rosa26LSL-tdTomato/+ mice were treated with tamoxifen (3 mg at either E10, E13, by oral gavage or a single intraperitoneal [i.p.] injection of 1mg at P0). Double fluorescence in situ hybridization for tdTomato (red) and TrkB (green) on thoracic DRG sections from P21 mice reveals that virtually all tdTomato+ DRG neurons are TrkB+ (100%, 194/194). A small subset of TrkB+ cells observed by in situ hybridization (green) are not labeled with the TrkBCreER labeling strategy (3/27 in this particular image). Scale bar represents 100 um.(B) Intracellular ex vivo electrophysiological recordings from a TrkBGFP-labeled Aδ-LTMR reveal selectivity of response to repetitive stimulation of a small cluster of hairs in the rostrocaudal direction; note the consistently greater response elicited by deflections in the rostral (R) versus caudal (C) direction.(C) Examples of responses to deflection of three different single hairs in the receptive fields of Aδ-LTMRs in K5Cre/+; BDNFflox/+; TrkBGFP/+ mice.(D) Vector plot of average responses to multiple deflections of a single hair in the four cardinal directions.(E) Examples of different vector plots elicited by movements of hairs in the receptive fields of Aδ-LTMRs in K5Cre/+; BDNFflox/+; TrkBGFP/+ mice (green, single hairs; orange, hair doublets; purple, cluster).(F) In vivo electrophysiological recordings of Aδ-LTMRs in trigeminal ganglia of TrkBCreER/+;Rosa26LSL-tdTomato/+ mice showing two different examples of responses elicited by controlled deflections of single hairs.(G) Examples of vector plots of average responses to multiple deflections of single hairs in the four cardinal directions in trigeminal Aδ-LTMRs in vivo.(H) Cumulative vector plot of all individual locations analyzed throughout the receptive fields of trunk and trigeminal Aδ-LTMRs in vivo, revealing a similar tuning for rostral deflections of hairs as in trunk DRG. Shown are the means ± SD. Scale bars represent 25 mV (B, C, and G), 250 ms (B and C), and 100 ms (G). See also .

(A and B) Ex vivo intracellular recordings of Aδ-LTMR responses elicited by deflecting a small cluster of hairs in (A) K5Cre/+; BDNFflox/+; TrkBGFP/+ control mice, and (B) K5Cre, BDNFflox/flox; TrkBGFP/+ mutant mice; note the selective tuning in the opposite, caudal direction in the latter.(C) Examples of responses to controlled deflection of three different single hairs in the receptive fields of Aδ-LTMRs in K5Cre; BDNFflox/flox; TrkBGFP/+ (mutant) mice.(D) Vector plot of average responses to multiple deflections of a single hair in the four cardinal directions and examples of different vector plots elicited by movements of single hairs in the receptive fields of Aδ-LTMRs in K5Cre; BDNFflox/flox; TrkBGFP/+ mice. Note the random, whorled orientations compared to controls ().(E) Shown are the means ± SD of spike numbers obtained from recordings of six neurons of each genotype, with responses to deflections of hairs in 60 and 45 individual locations from mutant and wild-type mice, respectively. Cumulative vector plot of all individual locations analyzed throughout the receptive fields of Aδ-LTMRs in K5Cre; BDNFflox/flox; TrkBGFP/+ mice (orange); note that the average response of all hairs combined lacks the direction-selective tuning observed overall in Aδ-LTMRs from control mice (blue). The latter represent replotted data from the ex vivo recording results from control mice, shown in .See also .